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cx3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation

Chinese Medical Journal 2022年第2期135卷 205-215页

作者： Jiawei Xin Chao Wang Xiaojuan Cheng Changfu Xie Qiuyang Zhang Yilang Ke Xuanyu Huang Xiaochun Chen Xiaodong Pan Department of Neurology Fujian Institute of GeriatricsFujian Medical University Union HospitalFuzhouFujian 350001China Fujian Key Laboratory of Molecular Neurology Fujian Medical UniversityFuzhouFujian 350001China Key Laboratory of Brain Aging and Neurodegenerative Diseases Fujian Medical UniversityFuzhouFujian 350001China School and Hospital of Stomatology Fujian Medical UniversityFuzhouFujian 350001China Department of Geriatrics Fujian Institute of GeriatricsFujian Medical University Union HospitalFuzhouFujian 350001China Fujian Key Laboratory of Vascular Aging Fujian Medical UniversityFuzhouFujian 350001China.

Background:Microglia plays an indispensable role in the pathological process of sleep deprivation(SD).Here,the potential role of microglial cx3C-chemokine receptor 1(cx3cr1)in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning.In this study,we aimed to investigat whether the interference in the microglial function by the cx3cr1 knockout affects the CNS's response to SD.Methods:Middle-aged wild-type(WT)C57BL/6 and cx3cr1^(−/−)mice were either subjected to SD or allowed normal sleep(S)for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night.After which,behavioral and histological tests were used to explore their different changes.Results:cx3cr1 deficiency prevented SD-induced cognitive impairments,unlike WT groups.Compared with the cx3cr1^(−/−)S group,the cx3cr1^(−/−)SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus(DG),decreased expression of pro-inflammatory cytokines,and decreased microglial phagocytosis-related factors,whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.Conclusions:These findings suggest that cx3cr1 deficiency leads to different cerebral behaviors and responses to SD.The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates,which indicate cx3cr1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

关键词： Sleep deprivation Cognitive dysfunction Microglia cx3cr1 deficiency

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